Lipid droplets-targetable fluorescent probe for monitoring polarity changes during ferroptosis

Ferroptosis, a form of regulated cell death driven by the accumulation of reactive oxygen species-induced lipid peroxide, has gained significant attention in various pathological contexts. Lipid droplets polarity may be affected and changed in the initiation and progression of ferroptosis. Therefore, developing a promising tool for high-fidelity fluorescence analysis and the early diagnosis of ferroptosis-associated diseases are very significant. Based on this, we prepared carefully two kinds of small-molecule fluorescent probes for detecting polarity. One of the fluorescent probes (PY-2), triphenylamine (an electron donor) and 3-benzofuranone (an electron acceptor) were effectively linked via a π bridge. In vitro experiments, the two probes showed high selectivity for environmental polarity over viscosity. The PY-2 precisely accumulated within lipid droplets in the colocation experiments, owing to its unique structural design. Additionally, the PY-2 exhibited low cytotoxicity, making it an ideal candidate for visualizing lipid droplets behavior during ferroptosis. Overall, this study offers a novel lipid droplets-targeting fluorescent probe (PY-2) to monitor polarity variations of lipid droplets during ferroptosis.